Inclusion Criteria:

• ≥ 12 years of age and weighing at least 40 kg at the time of informed consent.
• Signed an informed consent (and assent, as applicable, for minors) prior to any study related procedures.
• Willing and able to comply with protocol requirements.
• Progressive meningioma that is at least 1 cm3 and amenable to volumetric analysis and have not received any intervention or systemic therapy since the last progression event
  • Progressive tumor is defined as an increase in target meningioma volume of ≥ 20% within the 12 months prior to study enrollment;
  • For subjects receiving prior radiation, surgery, or other systemic therapy, progression would be documented from the time the last intervention was discontinued. In all cases, an MRI obtained within the prior 12 months or following a therapeutic intervention must be available and be reviewed by the central reader in parallel with the screening MRI to ensure the presence of progressive disease.
• Has either:
  • Sporadic meningioma with prior tumor analysis demonstrating NF2 mutation (at least one loss of function pathogenic variant in NF2); or
  • A confirmed diagnosis of NF2 disease by fulfilling the revised Manchester criteria, or having at least one NF2-related tumor (i.e., vestibular schwannoma, meningioma or ependymoma) and a pathogenic germline or proven mosaic NF2 variant.
• For participants with sporadic meningioma, the tumor must be either:
  • WHO Grade 1; or
  • WHO Grade ≥ 2 but not amenable to surgery or radiotherapy; or
  • WHO Grade ≥ 2 but the participant is not willing to undergo surgery or radiotherapy.
• No contraindication to MRI or intravenous contrast and is willing and able to undergo regular MRI scans with a contrast agent injection. Participants with an auditory brainstem implant or a cochlear implant can be included as long as the target tumor can be accurately measured volumetrically, without an artifact due to implant that affects the measurement of the target tumor.
• Karnofsky Performance Status (KPS) (age ≥ 16 years) or Lansky Performance Status (LPS) (for participants age < 16 years) ≥ 60 at screening.
• Adequate bone marrow function defined by all of the following at screening:
  • Peripheral absolute neutrophil count ≥ 1500/μL.
  • Platelet count ≥ 100,000/μL (transfusion independent, defined as not receiving platelet transfusions within a 3-month period prior to screening).
  • Hemoglobin ≥ 9 g/dL (participant may receive red blood cell transfusions).
• Adequate renal function, defined as estimated glomerular filtration rate (GFR) ≥ 60 ml/min/1.73 m^2 as calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
• Adequate liver function defined by both of the following at screening:
  • Total bilirubin ≤ 1.5 × upper limit of normal (ULN) for age (in participants with known Gilbert’s syndrome ≤ 3 × ULN for age).
  • Aspartate aminotransferase (serum glutamic-oxaloacetic transaminase) and alanine aminotransferase (serum glutamic pyruvic transaminase) < 3 × ULN for age.
• Discontinued all hematopoietic growth factors for at least 3 months prior to screening (e.g., filgrastim, sargramostim, and erythropoietin).
• Life expectancy of > 6 months, as determined by the investigator.
• Female participants who are women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours before the first dose of IMP and be willing to follow the contraceptive guidance in the protocol. If the urine test is positive or cannot be confirmed negative, a serum pregnancy test will be required and must be negative for the participant to be eligible.
• All participants must be willing to follow the contraceptive guidance in the protocol.

Exclusion Criteria:

• Progressive disease associated with significant or disabling clinical symptoms likely to require surgery or radiation therapy within the next 3 months.
• Received prior surgery, radiotherapy/stereotactic radiosurgery, or laser interstitial thermal therapy in the target tumor, or immediately adjacent to the target tumor in the last 6 months before screening.
• Received bevacizumab or another monoclonal antibody within the last 6 months, or everolimus, lapatinib, or another chemotherapeutic agent for meningioma in the last 3 months, or less than 5 half-lives (whichever is longer), prior to screening.
• History of an active malignancy within the previous 3 years except for localized cancers that are considered cured, and, in the opinion of the investigator, present a low risk of recurrence. These exceptions include, but are not limited to, basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast. Participants with any NF2 related tumors are allowed in the study.
• Received another investigational drug within 30 days prior to screening, or within a period during which the investigational drug has not been cleared from the body (e.g., a period of 5 half-lives), whichever is longer.
• Received prior treatment with REC-2282 or another HDAC inhibitor, including valproic acid within 3 years prior to Screening.
• Use of prescription drugs, over-the-counter drugs, and herbal supplements that are strong inhibitors or inducers of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A for 2 weeks prior to the start of the study and for the duration of the study, unless approved for use by the medical monitor.
• Pregnant, lactating, or is planning to attempt to become pregnant or impregnate someone during this study or within 90 days after the last dose of IMP.
• Use of contraceptive agents containing progesterone for one ovulation/menstruation cycle prior to the start of the study and for the duration of the study (including follow-up).
• Corrected QT interval using Fridericia’s formula of > 450 msec in men and > 470 msec in women at screening and at pre-dose on Cycle 1 Day 1.
• Severe or uncontrolled intercurrent illness or clinically significant unrelated systemic illness that, in the opinion of the investigator, could compromise participation in the study, including, but not limited to, symptomatic congestive heart failure or cardiomyopathy, uncontrolled hypertension, active bleeding diatheses, hemolytic anemia, uncontrolled diabetes, severe malnutrition, chronic severe liver or renal disease, unstable or new-onset angina pectoris, cardiac arrhythmia, autoimmune inflammatory diseases, significant cardiac, pulmonary, hepatic or other organ dysfunction, or psychiatric illness/social situations.
• Presence of an active and clinically relevant central nervous system disorder such as uncontrolled epilepsy, uncontrolled generalized seizure disorder, dementia, Parkinson’s disease, or organic brain syndrome. Note: participants with epilepsy may be enrolled if they are receiving non-enzyme inducing anticonvulsants, and seizures are well controlled. Peripheral neuropathy is not an exclusion.
• Any of the following known active infections:
  • Human immunodeficiency virus (HIV) not optimally controlled or treated. Participants with HIV who are on sustained stable antiretrovirals (for >4 weeks) and have CD4+ counts ≥ 350 cells/μL may be enrolled;
  • Chronic hepatitis B virus (HBV) infection with surface antigen positive. Participants with a prior history of treated HBV infection who are hepatitis B surface antigen-negative may be enrolled;
  • Chronic hepatitis C virus (HCV) infection- untreated or on active treatment. Participants with a prior history of treated HCV infection who are HCV RNA-undetectable may be enrolled;
  • Active infections requiring intravenous antibiotics within 2 weeks prior to randomization;
  • Any other known chronic active infection that requires ongoing treatment for the infection.
• Unable to swallow tablets.
• Clinically significant substance use disorder, as assessed by the investigator.
• Bone marrow or a solid organ transplantation within 5 years.
• Receiving immunosuppressive therapy.
• Major surgery within 4 weeks of screening. Portacath insertion, gastric tube placement, and insertion of ventriculoperitoneal shunt are not considered major surgeries for the purposes of this study.
  • Note: for participants with ventriculoperitoneal shunts, approval of tumor evaluability by central radiology imaging is required.
• History of allergic reaction to REC-2282 or its excipients.
• Has received > 2 mg dexamethasone or equivalent in the 4 weeks prior to screening.

Eligibility last updated 12/14/21. Questions regarding updates should be directed to the study team contact.